德国柏林查理特大学医学院Christian M. T. Spahn和美国伊利诺伊大学芝加哥分校Miljan Simonovi课题组合作，解析了哺乳动物核糖体解码硒代半胱氨酸 (Sec)UGA密码子时的结构。相关论文发表在2022年6月17日出版的《科学》杂志上。

他们使用冷冻电镜来观察哺乳动物中的 Sec UGA 重新编码。非编码 Sec 插入序列 (SECIS)、SECIS 结合蛋白 2 (SBP2) 和 40S 核糖体亚基之间的复合物使 Sec 特异性延伸因子 eEFSec 能够传递 Sec。eEFSec 和 SBP2 不直接交互，而是部署它们的羧基末端域以与 SECIS 的相对端接合。

通过使用其富含赖氨酸和羧基末端的片段，核糖体蛋白 eS31 同时与 Sec 特异性转移 RNA (tRNASec) 和 SBP2 相互作用，从而进一步稳定组装。eEFSec 无差别地对待 L-丝氨酸，并促进其在 Sec UGA 密码子中的错误结合。他们的结果支持真核生物中 Sec UGA 重新编码与细菌中的完全不同的机制。

据了解，真核生物硒蛋白的延伸依赖于将框内 UGA 终止密码子翻译为Sec的过程知之甚少。

附：英文原文

Title: Structure of the mammalian ribosome as it decodes the selenocysteine UGA codon

Author: Tarek Hilal, Benjamin Y. Killam, Milica Grozdanovi, Malgorzata Dobosz-Bartoszek, Justus Loerke, Jrg Bürger, Thorsten Mielke, Paul R. Copeland, Miljan Simonovi, Christian M. T. Spahn

Issue&Volume: 2022-06-17

Abstract: The elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec UGA recoding in mammals. A complex between the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and 40S ribosomal subunit enables Sec-specific elongation factor eEFSec to deliver Sec. eEFSec and SBP2 do not interact directly but rather deploy their carboxyl-terminal domains to engage with the opposite ends of the SECIS. By using its Lys-rich and carboxyl-terminal segments, the ribosomal protein eS31 simultaneously interacts with Sec-specific transfer RNA (tRNASec) and SBP2, which further stabilizes the assembly. eEFSec is indiscriminate toward L-serine and facilitates its misincorporation at Sec UGA codons. Our results support a fundamentally distinct mechanism of Sec UGA recoding in eukaryotes from that in bacteria.

DOI: abg3875

Source: https://www.science.org/doi/10.1126/science.abg3875